As part of UK Pride month, we are spotlighting the work of cancer researcher and University LGBTQ+ Representative Dr Eoghan Mulholland
We are proud to announce that renowned immunologist Lieping Chen is joining the Oxford Branch of the Ludwig Institute for Cancer Research, Nuffield Department of Medicine, as a Visiting Professor of Cancer Immunotherapy. Chen, who is the United Technologies Chair in Cancer Research, a Professor of Immunobiology, Medicine and Dermatology, and co-director of the Cancer Immunology Program at Yale Cancer Center, Yale University School of Medicine, USA, is an international leader in basic T cell biology and cancer immunotherapy. His visiting professorship at Oxford opens new opportunities for collaboration and expansion in this crucial field.
Cancer immunotherapy is now poised to become a standard treatment for cancer, alongside surgery, chemotherapy, radiotherapy and targeted therapy. Chen has contributed enormously to this exciting development through his seminal work on the PD-1/PD-L1 immune suppressive pathway. The concept of turning a patient’s own immune system against a tumour was proposed decades ago, but it has only recently become a reality. The most effective immunotherapy approach to date involves the blockade of the PD-1/PD-L1 pathway.
Chen discovered PD-L1 (originally termed B7-H1) as a member of the B7 family of ligands that have immune suppressive functions. He also demonstrated that human tumours express high levels of PD-L1, and that forced expression of PD-L1 in murine tumours confers resistance to immune elimination. Further, he showed that anti-PD-L1 antibodies could block the interaction of PD-L1 with its receptor (PD-1) to undermine this immune resistance. This revealed the importance of the PD-1/PD-L1 pathway in tumour immune resistance and put this pathway on the map as a target for cancer therapy.
Chen has continued to contribute to the clinical targeting of the PD-1/PD-L1 pathway. He developed an immunohistochemistry assay for PD-L1 detection in human cancer tissues and collaboratively demonstrated that PD-L1 expression in tumours predicts a greater response to anti-PD-1/PD-L1 therapy. He also helped to initiate and organise the first-in-human clinical trial of a therapy targeting PD-1/PD-L1 pathway.
Chen has received several awards and honours in recognition of his outstanding scientific achievements, including the William B. Coley Award (2014), AAI-Steinman Award (2016), Warren Alpert Foundation Prize (2017), Giants of Cancer Care (2018) and Richard V. Smalley Award (2020). He is a member of the National Academy of Sciences USA and a Fellow of the AACR Academy, American Association for Cancer Research.
The Academy of Medical Sciences has elected 11 University of Oxford biomedical and health scientists to its fellowship this year. All were selected for their exceptional contributions to the advancement of medical science through innovative research discoveries and translating scientific developments into benefits for patients and the wider society.
OxCODE Associate Director Professor David Hunter (Nuffield Department of Population Health) is elected as a Fellow for his leading role in HIV and later cancer research. A highly cited scientist, he has been involved in collaborative studies of nutrition and HIV pathogenesis, studied diet and cancer aetiology in large scale prospective studies, and developed a sample handling and genotyping laboratory to explore genetic associations with cancer, and gene-environment interactions.
Professor Hunter said ‘As someone born in the UK, having grown up and gone to medical school in Australia, and having spent most of my career in epidemiology in the US, I am deeply honoured to be elected to the Academy, and look forward to participating in the important work the Academy does on behalf of UK and global medical science.’
The Academy of Medical Sciences is the independent body in the UK representing the diversity of medical science. Elected Fellows are the UK’s leading medical scientists from hospitals, academia, and industry. They are recognised for their innovative research discoveries and for translating scientific developments into benefits for patients and wider society. This year, 50 Fellows were chosen from 384 candidates.
The new Fellows will be formally admitted to the Academy on 1 July 2021. For details of the other Fellows elected this year, please visit the Academy of Medical Sciences website.
Professor Adrian Hill, Director of the Jenner Institute (Nuffield Department of Medicine), has become a Fellow of the Royal Society for his leading role in the design and development of new vaccines for globally important infectious diseases over the course of over 25 years.
One of his most important developments has been the spin out of Vaccitech, which he co-founded in 2016, to capitalise on the discovery of ChAdOx. The chimp cold virus, ChAdOx, became a weapon of choice against what the World Health Organization called “Disease X” – a hypothetical future pathogen with epidemic or pandemic potential.
ChAdOx is a viral vector which safely mimics viral infection in human cells and elicit antibody and T cell responses to pathogens and tumours. Thus far, ChAdOx has already been applied in cancers (prostate), malaria, and most recently, the AstraZeneca-Oxford vaccine for Sars-Cov-2.
Through his work, Professor Hill has demonstrated the applications of adenoviruses in immunisation regimes supporting new vaccination approaches for a variety of disease, many of which have previously not had treatment options available.
Professor Hill becomes one of 6 new Oxford researchers to join the Royal Society. Read about them here.
Immune related toxicity is a common side effect of treatment with Immune Checkpoint Blockers for cancer – but the degree to which the development of these side effects is related to overall oncological outcome is unclear. As an Academic Foundation Programme Trainee within OUCAGS (https://www.oucags.ox.ac.uk), I had a four month block of time to work in a lab to gain experience of research. I worked with Dr Benjamin Fairfax’s group in the WIMM/Department of Oncology to explore the relationship between immune toxicity and clinical outcomes. Working with other members of the group, and Dr Anna-Olsson Brown in Liverpool, we found that patients who developed immune related toxicity appeared to have better long-term clinical outcomes including overall survival. Indeed, we found the development of toxicity was a key predictor of the cancer responding to treatment. This work is currently in-press in the British Journal of Cancer.
This period of time in the lab stimulated my interest in research and helped in my decision to apply for an Academic Clinical Fellowship in Dermatology. I was successful in this and I have a further nine months of protected research built into my training this year, which I again plan to spend working in Ben’s group. As a trainee dermatologist I am particularly intrigued by the rash patients frequently develop when they first receive immunotherapy. There is evidence to suggest that another side effect of immunotherapy, colitis, is secondary to the activation of resident memory T cells. Conversely, when you look at the gene expression in CD8 T cells after treatment with checkpoint blockers you can see up-regulation of genes involved in skin trafficking. I will explore whether this rash is indicative of T cell trafficking to the skin, or activation of resident memory T cells, or something completely separate.
Cancer Research UK awards biannual pre-doctoral research bursaries, aimed at providing ‘short term funding to allow clinicians and other health professionals to get involved in research projects early in their career’. Ben encouraged me to apply to this CRUK scheme to further explore the mechanistic basis of the rash in immunotherapy and I am very grateful to have been awarded this funding. Personally I am hoping to gain training in immunological techniques and bioinformatic analysis during this period, and I hope the results we generate will provide further insights into the cells cancer immunotherapy affects and how it works.
The CRUK Oxford Centre is pleased to announce the appointment of Professor Tim Elliott as its new co-Director. Tim will work alongside Professor Mark Middleton who has filled the role since 2017, to develop and deliver the research strategy for the Oxford Centre.
Professor Tim Elliott is taking over from Professor Xin Lu, who is stepping down after over 3 successful years in the post. During her tenure, Xin has led a step change in the coordination and integration of research efforts across the city. Under Xin’s leadership, a collaborative network of early cancer detection researchers across Oxford has been established and supported through the formation of the Oxford Centre for Early Cancer Detection (OxCODE). As well as providing a forum to stimulate and catalyse research in this critically important research field, significant programmatic funding has been obtained, including for liver (DeLIVER – Prof. Ellie Barnes) and lung (DART – Prof. Fergus Gleeson) cancers, along with numerous seed and project external funding awards in early detection. Xin will continue to play a major role in directing and supporting the CRUK Oxford Centre strategy in her continuing positions as OxCODE Director, NIHR Oxford BRC Cancer Theme Co-Lead and Director of the Ludwig Institute for Cancer Research, Oxford Branch.
Tim has recently joined the Nuffield Department of Medicine and Oriel College as the Kidani Professor of Immuno-Oncology. He re-joins the Oxford community from Southampton University, having previously completed his undergraduate degree in Biochemistry at Balliol and subsequently holding a Professorial post at the Weatherall Institute for Molecular Medicine. Tim brings with him a wealth of expertise and experience in leading international collaborative multidisciplinary research; and he helped lead the campaign for the Southampton Centre for Cancer Immunology which opened in 2018 and where he was Director until his appointment in Oxford. He is ideally placed to help lead the Oxford Centre in its efforts to ensure that cancer research across the city continues to drive improvements in cancer patient care through enhancing our fundamental understanding of the disease.
Professor Tim Elliott, Cancer Research UK Oxford Centre Co-director and Kidani Professor of Immuno-Oncology at the Nuffield Department of Medicine, University of Oxford, said:
“This is a great time to be joining Oxford. Recent events have demonstrated how effectively Oxford researchers can come together to generate the new knowledge needed to drive life-saving treatments for a new pathogen. There is every sign that we can focus that collegiality on beating cancer too.
“I am excited by the prospect of helping multidisciplinary teams to converge on difficult problems that will ultimately lead to better clinical outcomes for people diagnosed with cancer. I am also really looking forward to working with Mark, whose clinical and translational expertise and great leadership will be key to pulling our discovery science through into the clinic.”
Professor Mark Middleton, Cancer Research UK Oxford Centre Co-director and Head of Department of Oncology at the University of Oxford, said:
“I am delighted that Tim will help lead our diverse research community. His successful approach to delivering internationally recognised multi-disciplinary immunology research makes him an exciting addition to Oxford. Tim joins us a fascinating time, with more opportunities than ever for ensuring that cancer patients benefit from the world-leading research being carried out across Oxford. His track record of bringing together fundamental, translational and clinical researchers that span traditional research boundaries will be critical in building on our recent progress exploiting Oxford’s cancer research ecosystem to improve patient care worldwide.
“The leadership Xin has provided to the Cancer Centre over the last 3 years has been transformative. There are many clinical trials and early detection programmes that would not have taken place without her, and this is testament to both her strategic vision and the time and effort she has put into the Centre during her tenure. I’d like to thank Xin on behalf of all the researchers across Oxford who have benefited from her leadership. I look forward to continuing to work with her on delivering the Centre’s goals in her capacity as OxCODE Director, NIHR Oxford BRC Cancer Theme Co-Lead, and Director of the Oxford Branch of the Ludwig Institute for Cancer Research.”
A very warm welcome to Professor Tim Elliott from the CRUK Oxford Centre team and wider cancer research community here in Oxford.
Professor Tim Elliot Biography
Professor Tim Elliott left the University of Oxford with a first in Biochemistry in 1983, received a PhD from the University of Southampton in 1986 and completed his postdoctoral training at MIT. He held a lectureship and later a professorship in immunology (Weatherall Institute for Molecular Medicine and Balliol College, University of Oxford) between 1990-2000 before being appointed to the Chair of Experimental Oncology, School of Medicine, University of Southampton.
He was Associate Dean (Research) for the Faculty of Medicine between 2005 and 2015. He’s held appointments on Scientific Advisory boards at the Wellcome Trust, the Association of International Cancer Research, Leukaemia and Lymphoma Research, Symphogen, and Avviity Therapeutics; chairs the CRUK Expert Review Group for Cancer Immunology and sits on the CRUK Discovery Science Research Committee. He has published over 130 papers in the field of molecular immunology; was visiting lecturer of the Alberta Heritage Foundation for Medical Research, University of Edmonton, Alberta in 1999; and recently held a visiting Professorship at the Netherlands Cancer Institute, Amsterdam. He is a fellow of the Royal Society of Biology and in 2014 he was elected to the Academy of Medical Sciences.
Professor Elliott was amongst the key group of immunologists who developed studies of antigen presentation at the molecular level during the 1990s, undertaking a series of studies to determine and define the immunostimulatory properties of MHC Class I molecules and elucidating the molecular mechanisms of co-factor assisted peptide loading of MHC Class I in antigen presenting cells: work considered to be the foundation of much of the recent work on antigen presentation. The work underpins rational T-cell based vaccine design and continues to fuel translational research where discoveries in the areas of antigen discovery, T cell regulation and immunodominance are making a significant impact on new and ongoing cancer immunotherapy trials.
His mechanistic studies have always benefitted from an active interface with the physical sciences, mathematics and computer science, nanofabrication and engineering.
Yang Shi, who joins Ludwig from Harvard University, is a world leader in the field of epigenetics, which explores how chemical modifications to chromatin—the combination of DNA and histone proteins—control the organisation and expression of the human genome. Aberrations in those processes are vital drivers of cancer and underlie many other diseases and disorders.
“Yang has an outstanding track-record of innovative research into the identity and mechanisms of action of chromatin modifiers. We are delighted that Yang is bringing his wealth of experience, international standing and collaborative spirit to lead our cancer epigenetics theme at Ludwig Oxford.”
~ Xin Lu, Director of the Ludwig Oxford Branch.
Shi is widely known for his discoveries regarding a chemical modification, methylation, made to the histone proteins. In 2004, Shi and his colleagues identified and characterised an enzyme, LSD1, that erases methyl marks from histones. Their discovery upended a 40-year-old dogma that considered such modifications irreversible, altering longstanding models of genomic regulation. Shi’s laboratory went on to identify many other histone demethylating enzymes with roles in a diverse array of biological processes. More recently, his group discovered several enzymes that methylate RNA and possibly influence the translation of gene transcripts into proteins.
Shi is applying these fundamental discoveries to the benefit of patients. His group’s work on LSD1 led to the development of LSD1-inhibitors now in clinical trials for the treatment of cancer. More recently, Shi and his colleagues demonstrated that inhibiting LSD1 might also help make otherwise non-responsive tumours susceptible to the checkpoint blockade immunotherapy. His lab is additionally studying the role and therapeutic manipulation of epigenetic modifiers in pediatric high-grade gliomas and acute myeloid leukaemia.
“Yang’s science is of the highest calibre—as rigorous and collaborative as it is original—and we are very excited to have him in the Ludwig community. I’m sure many of our researchers will benefit from his expertise, and that they will be equally generous with their own expertise and support as he explores the implications of his discoveries for cancer biology and the design of new therapies.”
~ Chi Van Dang, Scientific Director of the Ludwig Institute.
Shi obtained his PhD from New York University, completed his postdoctoral training with Thomas Shenk of Princeton University and joined the faculty of Harvard Medical School in 1991, where he was most recently C.H. Waddington Professor of Pediatrics. Shi has received many honours for his contributions to epigenetics and is a fellow of the American Association for the Advancement of Science and a member of the American Academy of Arts and Sciences.
Eileen brings research into the body’s innate immune response to cancer and how we can harness these pathways to develop novel clinical treatments
Sir Peter joins the ranks of the American Association for Cancer Research’s finest scientists.
The Royal Society, the UK’s distinguished academy of science, has announced the election of 62 new Fellows and Foreign Members, which include Professor Xin Lu FMedSci FRS. Xin is the current co-director of the CRUK Oxford Centre and Director of the Oxford branch of the Ludwig Institute for Cancer Research. It has been Xin’s distinguished career as a cancer biologist and her contributions to the understanding of cellular pathways that control cell fate in development and disease, particularly cancer, has earnt her this accolade.
She has a long-standing interest in how to selectively kill cancer cells, and her major research advances have provided insights into how p53, the most mutated or inactivated tumour suppressor in human cancers, can make life or death decisions for a cell. Xin’s early work showed how p53 responds to activation of cancer-causing genes and DNA damage. She has since discovered the ASPP family of proteins as molecular switches that control p53-mediated cell killing. Find out more about Xin’s research here.
Xin’s impact on the cancer landscape in Oxford
Of equal importance is the impact that Xin has had on the cancer research community here at Oxford. Her ability and desire to bring researchers together across traditional thematic boundaries was one of the many reasons she was appointed to the Cancer Research UK Oxford Centre Management Group in 2016 and as co-Director in 2018. During this time, her ability to identify new opportunities for collaboration and galvanise research teams from multiple corners of both the University and Hospital, has impacted both Oxford’s Oesophageal Cancer and Early Cancer Detection communities.
“It’s fantastic that Xin’s academic work has been recognised in this way” said Professor Mark Middleton, co-Director of the Cancer Research UK Oxford Centre.
“We are fortunate in Oxford to have a scientist of Xin’s calibre who is so committed to making sure that our world class science improves patient care. Many of the achievements of the Oxford Centre in recent years would not have been possible without her drive and leadership. Her ability to engage and energise research teams has had a profound impact on the cancer research community at the University and Trust, that will be felt for years to come.”
The fruits of these efforts are numerous and include Oxford being selected to host the inaugural CRUK International Symposium on Oesophageal Cancer; engaging with local clinicians to drive the opening of numerous innovative clinical and experimental medicine studies in upper GI cancers (including LUD2015-005 to test novel combinations of radiation-, chemo- and immune- therapy in this setting), the launch of the Oxford Centre for Early Cancer Detection and the external funding of numerous Oxford-ed project and programme awards in these fields.
“I am humbled to receive this honour from the Royal Society” said Professor Lu.
“As someone who barely spoke English at the beginning of my scientific career, I am hugely grateful for all the support I have received from my supervisors and mentors. My appreciation also goes to the Ludwig Institute for Cancer Research for its long-term research funding and to the Department, College and University for a supportive and creative environment. Most important of all, my deep gratitude goes to the fantastic scientists in my laboratory, and colleagues I’ve had the privilege to work with throughout my career to date, without whom this recognition would not have been possible.”
About the Fellowship
The Royal Society is a self-governing Fellowship dating back to the 1660s that is dedicated to promoting excellence in science for the benefit of humanity. The Fellowship comprises the most eminent scientists, engineers and technologists from the UK and the Commonwealth. Former members include Sir Isaac Newton, Charles Darwin, Albert Einstein, Dorothy Hodgkin and Stephen Hawking. This year, 51 Fellows, 10 Foreign Members and one Honorary Fellow have been elected for life through a peer review process on the basis of scientific excellence. There are approximately 1,700 Fellows and Foreign Members in total, including around 70 Nobel Laureates. These include Ludwig Oxford’s Professor Sir Peter Ratcliffe, a co-recipient of the 2019 Nobel Prize in Physiology or Medicine.
Venki Ramakrishnan, President of the Royal Society, said
“At this time of global crisis, the importance of scientific thinking, and the medicines, technologies and insights it delivers, has never been clearer. Our Fellows and Foreign Members are central to the mission of the Royal Society, to use science for the benefit of humanity. While election to the Fellowship is a recognition of exceptional individual contributions to the sciences, it is also a network of expertise that can be drawn on to address issues of societal, and global significance.
“This year’s Fellows and Foreign Members have helped shape the 21st century through their work at the cutting-edge of fields from human genomics, to climate science and machine learning. It gives me great pleasure to celebrate these achievements, and those yet to come, and welcome them into the ranks of the Royal Society.”
Six academics from Oxford have been honoured in this year’s round of Royal Society Fellowship elections. Find out more on the Royal Society website.